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Biomedical subjects

J Fujimoto

Publications and source records attributed to J Fujimoto.

At least 235 records · Page 13Linked to original sources

Expression of sex hormone-binding globulin mRNA in uterine leiomyoma, myometrium and endometrium of human subjects.

This study was designed to evaluate the effect of sex hormone-binding globulin (SHBG) on the estrogen-dependent growth of human uterine leiomyoma. Levels of SHBG mRNA were analyzed using competitive reverse transcription-polymerase chain reaction-Southern blot analysis (RT-PCR-SBA). In normal uterine endometria, the levels of SHBG mRNA in the early/mid and late proliferative phases of the menstrual cycle were significantly lower than in the secretory phase (p < 0.01). In uterine myometria and leiomyomas, SHBG mRNA level showed no significant differences during the menstrual cycle, while the ratio of leiomyoma SHBG level to the corresponding myometrium SHBG level was >1 in 21 out of 23 cases (91%). Our results suggest that steroidal regulation of intracellular SHBG synthesis in the myometrium and the leiomyoma might differ from that in the endometrium, and that the mechanism of SHBG expression in leiomyoma might, in the process of tumorigenesis, be altered from that of corresponding normal myometrium, contributing to SHBG overexpression and the abundant estrogen supply.

Adult↗

Clinical implication of fos and jun expressions and protein kinase activity in endometrial cancers.

Under the previous data of the presence of fos/jun expression via protein kinase C (PKC) activation by estrogen in endometrial cancer cell line (1), the following experiment was made on the endometrial cancer tissue of the human subject. The ratio of membrane/cytosol PKC activity and the level of fos/jun expression were significantly higher in well differentiated endometrial cancers than in those of moderately or poorly differentiated ones. Those two in the endometrial cancer were significantly higher than those in the normal counterpart. The ratio and the expression in normal uterine endometria of the proliferative phase were significantly higher than those in the secretory phase. Both in the endometria were significantly enhanced 1 week after the administration of estrogen. It is suggested that the linkage of fos/jun expression via PKC activation by estrogen might be exaggerated in the endometrial cancers, especially in the well differentiated, plausibly with the loss of the anti-estrogen effect of progesterone, but dedifferentiation might lose this linkage.

Adult↗

Preliminary study of oncogene expressions in endometrial cancers. Aberrant estrogen receptor gene and erbB-2 expressions.

We studied the expressions of aberrant epidermal growth factor receptor (EGFR) gene or erbB-2, which is highly homologous to EGFR gene, and erbA or estrogen receptor (ER) gene, which is highly homologous to erbA, as a preliminary study, to know which oncogene expressions are associated with the development of endometrial cancers. ErbB-2 mRNA lacked only extracellular domain (EX), suggesting the lack of downregulation of erbB-2 expression by a ligand, which led to regulated tyrosine kinase activity. Mutated DNA binding domain of ER mRNA were found in 3 of the 13 cases, suggesting the promotion disorder of estrogen-inducible proteins in these 3 endometrial cancers. The behavior of aberrant erbB-2 and ER gene co-expressions is considered of similar to that of erbA and erbB co-expressions in the chicken introduced by the avian erythroblastosis virus, which leads to the development of erythroblastosis in the chick, and seems to be associated with the development of endometrial cancer.

Adult↗

Hepatic resection under in situ hemihepatic hypothermic perfusion with hepatoprotective agents.

Hepatectomy was performed under in situ right lobar hypothermic perfusion combined with hepatoprotective agents in six patients who had hepatocellular carcinoma and coexisting liver disease. Following occlusion of the right hepatic vein and the right portal pedicle, in situ cold perfusion was initiated using chilled Ringer's lactate infused through a cannula placed in the right main portal vein. The right superior segments were resected in a bloodless field. The liver was cooled to 22-26 degrees C for 40 to 80 minutes with no significant changes in systemic hemodynamics or body temperature. Postoperative liver functions showed no marked derangement; the mean peak GPT was 221 U and the mean peak total bilirubin 2.3 mg d/l. Local cooling minimizes the risk of ischemia/reperfusion injury in this very vulnerable population, yet gives the surgeon adequate time to perform a challenging resection in a bloodless field.

Aged↗

Laparoscopic microwave coagulonecrotic therapy for hepatocellular carcinoma.

The present study reports on the usefulness of laparoscopic microwave coagulonecrotic therapy as a new option in the treatment of hepatocellular carcinoma. Five patients with liver tumors associated with cirrhosis were treated from July 1993 to March 1994 with a microwave electrode (output 100 W, 3 to 4 cm long) devised for laparoscopic use. The tumors, all with diameters less than 3 cm and superficially located, were coagulated for a total radiation period of 20 to 30 min under laparoscopic, intraoperative ultrasonographic control. Postoperative complications were negligible, and laboratory values (glutamate-pyruvate transaminase, bilirubin, prothrombin time, platelet count) returned to preoperative levels within 7 days. Complete necrosis, including the surrounding liver tissue, was confirmed by a follow-up dynamic computed tomography scan during the follow-up period of 6 to 17 months (mean, 13 months). Laparoscopic microwave coagulonecrotic therapy can exert an effect on tumor equivalent to that obtained from a wedge resection but is noninvasive and may represent a new option for unresectable liver cancers.

Aged↗

Estrogen activates invasiveness of endometrial cancel cells to the interstitium.

Invasiveness of endometrial cancer cells such as Ishikawa, HEC-1-A and HHUA cells, to the interstitium was significantly enhanced by estradiol, while medroxyprogesterone acetate (MPA) significantly diminished the estradiol-enhanced invasive potential. All of these endometrial cancer cells possess estrogen receptors. It is suggested that invasiveness to the interstitium, and consequently infiltration to the uterine myometrium (which means local advance) are activated by estradiol via a mechanism related to the estrogen receptor, and that MPA as an antiestrogen agent partly inactivates the invasive ability.

Cell Movement↗

Expression of basic fibroblast growth factor and its mRNA in uterine endometrial cancers.

to evaluate the potential of growth, invasion and metastasis of endometrial cancer cells associated with neovascularization, the expression of basic fibroblast growth factor (FGF) and its mRNA in endometrial cancers and normal endometria as controls was determined by enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction and Southern blot. the relationship between FGF expression and histological grades, and the degree of myometrial invasion or clinical stages of endometrial cancers were analyzed. The level of basic FGF was found significantly higher in endometrial cancers of G3 and stage III-IV compared to normal endometria. Likewise, the level of basic FGF mRNA was significantly higher in endometrial cancers of G3, level C and stage IV-IV compared to normal endometria. In cancers of other categories, G1 and G2, levels of A and B, and stage I evaluation in the levels of basic FGF and its mRNA did not differ significantly from those in normal endometria. Since lethal lesions are mostly confined to endometrial cancers of G3, level C, and stages III-IV, the increase of basic FGF, which leads to neovascularization, could be one of the characteristics of highly malignant and /or advanced endometrial cancers, and may contribute to the acceleration of growth, invasion, and metastasis.

Adult↗

Diagnosis of t(2;5)(p23;q35)-associated Ki-1 lymphoma with immunohistochemistry.

Some Ki-1 lymphomas carry a specific chromosomal translocation, t(2;5)(p23;q35). We have recently found a novel hyperphosphorylated 80-kD protein tyrosine kinase, p80, in a human Ki-1 lymphoma with this translocation. Subsequent cDNA cloning showed that p80 is a fusion protein of two different genes on chromosome 2p23 and 5q35, the novel tyrosine kinase gene and nucleophosmin gene, respectively. In this study, we intended to detect p80 on lymphoma tissues with immunologic methods. Thus, we developed rabbit polyclonal antibody using a synthetic peptide corresponding to a part of its kinase domain. The antibody (anti-p80) immunoprecipitated and immunoblotted p80 specifically from AMS3. Then, to examine whether t(2;5)(p23;q35) was present on biopsied lymphomas, reverse transcriptase-polymerase chain reaction (RT-PCR) covering the fusion junction of p80 mRNA was performed. Among 10 Ki-1 lymphomas and 10 additional lymphomas other than the Ki-1 lymphomas, expression of p80 mRNA was detected in three cases exclusively. When these 20 cases and additional 30 lymphomas were immunostained with anti-p80, positive staining was noted exclusively in the three cases found by PCR to have harbored the p80 mRNA. Thus, the present immunostaining, as well as PCR, was shown to be efficient for detecting lymphomas producing this chimeric protein/mRNA.

Amino Acid Sequence↗

Phorbol myristate acetate enhances degradation of TRH receptor mRNA in a pituitary cell type-specific manner.

Regulation of the level of thyrotropin-releasing hormone (TRH) receptor (TRH-R) mRNA appears to involve both modulation of gene transcription and of mRNA degradation. To study regulation of TRH-R mRNA degradation and circumvent any physiological effect on transcription, we use cells stably transfected with mouse TRH-R cDNA under control of the constitutively active cytomegalovirus promoter. In stably transfected GH pituitary cells, we find that phorbol 12-myristate 13-acetate (PMA), like TRH, down-regulates TRH-R mRNA by increasing the rate of TRH-R mRNA degradation. In contrast, in stably transfected AtT-20 pituitary cells and in nonpituitary cell lines, neither TRH nor PMA decreased TRH-R mRNA levels. These findings are consistent with the idea that activation of protein kinase C leads to enhanced degradation of TRH-R mRNA in a cell-type-specific manner.

Animals↗

Corticosteroid-binding globulin mRNA levels in human uterine endometrium.

Corticosteroid-binding globulin (CBG or transcortin) is a specific plasma glycoprotein, which binds steroid hormones (cortisol, corticosterone, and progesterone), and plays a role in transporting these steroids, altering their concentrations in blood, and influencing their biological actions. CBG has been previously shown to be synthesized in the liver, but recently it has been reported that immunoreactive CBG is localized in target tissues. In the present work, CBG mRNA was detected in normal human endometrial tissues by Northern blot analysis and reverse transcription-polymerase chain reaction. Its level was higher (P < 0.05) in the secretory phase than in the proliferative phase. In the secretory phase, the endometrial CBG mRNA level was negatively correlated with the serum progesterone level (P < 0.01). While there was no positive correlation between the levels of endometrial CBG mRNA and serum estradiol (E2), there was a positive correlation between the endometrial CBG mRNA level and the serum E2/progesterone ratio (P < 0.05). These findings suggest that CBG is synthesized in the uterine endometrium, predominantly in the secretory phase, and that the serum E2/progesterone ratio exerts an influence on the synthesis of intracellular CBG.

Adult↗

The effect of estrogen and androgen on androgen receptors and mRNA levels in uterine leiomyoma, myometrium and endometrium of human subjects.

This study was designed to show the effect of estrogen and androgen on the level of testosterone and dihydrotestosterone specific binding sites (TBS and DHTBS, respectively) and to clarify the implication of androgen receptor mRNA expression to TBS and DHTBS in human uterine tissues. Estrogen mainly induces the increase of TBS and androgen receptor mRNA in uterine endometrium and leiomyoma. TBS increased by estrogen are downregulated when testosterone is given along with estrogen, while androgen receptor mRNA increased by estrogen was not significantly altered by testosterone with estrogen in endometrium and leiomyoma. These results suggest that the androgen receptor mRNA determined might encode TBS and that testosterone may stimulate the metabolic rate of TBS, or inhibit the translation rate of androgen receptor mRNA to TBS. Furthermore, the biological character of leiomyoma is considered to be an endometrial type.

Adult↗

A prediction scoring system to select the surgical treatment of liver cancer. Further refinement based on 10 years of use.

OBJECTIVE: This study reports further refinement of a prediction scoring system, which was established in 1980 as a guide to determine a safe limit for hepatectomy, based on 10 years of use. SUMMARY BACKGROUND DATA: In the past, whether major resection was safe was judged empirically from the net resection volume or the residual hepatic volume combined with the patient's liver function. However, such judgment was not based on objectively defined criteria. METHODS: Patients with hepatocellular carcinoma (HCC; n = 376) and metastatic cancer (n = 58) who had hepatectomy at some time from 1981 through 1990 were entered into this study. A prediction score (PS) was computed using a multiple regression equation that consists of computed tomographic scan-estimated resection rate, indocyanine green retention rate, and the patient's age. A PS greater than 55 was classified as a risky zone, a PS of 45 to 55 was considered borderline and a PS less than 45 was a safe zone. RESULTS: With HCC and chronic liver disease, all patients in the risky zone died, whereas 33% in the borderline zone died and 7.3% died who were in the safe zone. With metastatic cancer with normal liver, all patients in the risky zone died, whereas no patient in either the borderline or safe zones died. The major cause of death in the risky zone was liver failure due to excessive resection. In the borderline and safe zones, liver failure developed primarily after abdominal sepsis or pulmonary infection, particularly for those with adverse prognostic factors such as disturbed glucose tolerance, lower platelet count, and higher indocyanine green retention rate. CONCLUSION: Prediction scores can eliminate deaths related to excessive resection for patients with normal or injured livers. When patients have adverse prognostic factors, careful surgery and postoperative management is mandatory to avoid liver failure triggered by intra- or extra-abdominal sepsis, even if the score remains in a borderline or safe zone.

Aged↗

Expression of aberrant estrogen receptor mRNA in endometrial cancers in comparison with normal endometria.

In endometrial cancers, some overexpression of estrogen receptor (ER) mRNA occurred in comparison with the ER mRNA level in normal endometria. DNA binding domains (DBDs) of ER mRNA were detected in 100% (13/13) of the endometrial cancers, and a mutated ER-DBD mRNA was found in 3 of the 13 by S1 nuclease protection analysis. It is suggested that estrogen might lead to disorder in the promotion of estrogen-inducible proteins in these 3 endometrial cancers, which seem to have a point-mutated DBD of the ER and a functional steroid-binding domain, resulting in the dedifferentiation of the original cells, and that the development and growth of cancer cells might, in part, be driven by estrogen.

Adult↗

Tissue differences in the expression of mRNAs of Ha-ras, c-myc, fos and jun in human uterine endometrium, myometrium and leiomyoma under the influence of estrogen/progesterone.

Ha-ras expression level in uterine endometrium (EM) in the proliferative phase (PP) was significantly higher than that in the secretory phase (SP). c-myc expressions were detected in EM, uterine myometrium (MM) and uterine leiomyoma (LM) without any cyclic change; fos expressions in LM, MM, and EM were detectable in PP, but not in SP. jun expression level in LM was significantly higher than that in MM and EM in PP, but did not alter during the menstrual cycle. Estrogen elevated the levels of Ha-ras and fos mRNAs in the three tissues, jun mRNA in MM and EM, and c-myc mRNA in LM and MM. These results suggest that there is a tissue difference in the expression of Ha-ras, c-myc, fos and jun among EM, MM and LM, under the influence of estrogen/progesterone.

Adult↗

Sex hormone-binding globulin mRNA levels in human uterine endometrium.

Sex hormone-binding globulin (SHBG) is a specific steroid hormone-binding protein that plays a role in transporting dihydrotestosterone, testosterone and estradiol-17 beta (E2), altering their concentration in blood and influencing their biological action. Recently it has been reported that immunoreactive SHBG is localized in target tissues and that SHBG mRNA was identified in human endometrial and prostatic cell lines. In the present work, SHBG mRNA was detected in human normal endometrial tissues using Northern blot analysis and polymerase chain reaction. Its level was higher (p < 0.02) in the secretory phase than in the proliferative phase. In the secretory phase, the endometrial SHBG mRNA level was correlated positively with serum E2 and progesterone level (p < 0.05). However, there was a negative correlation between endometrial SHBG mRNA level and serum E2/progesterone ratio (p < 0.01). These findings suggest that SHBG is synthesized in the uterine endometrium and a part of its synthesis is regulated complexly by sex steroid hormones such as E2 and progesterone.

Adult↗